Hyperuricemia aggravates acute colitis through NLRP3-associated macrophage-lineage inflammatory responses

Clicks: 13
ID: 337432
2026
Free PDF
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Emerging

Ranked #93 of 100 articles by views in inflammatory bowel diseases

Most read Least read

Bar heights use a square-root scale.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
Abstract Background Inflammatory bowel diseases (IBDs) are chronic, relapsing inflammatory disorders of the gastrointestinal tract with rising prevalence. Hyperuricemia has been associated with IBD, but whether elevated uric acid (UA) directly aggravates intestinal inflammation and how it affects immune responses remain unclear. Methods We used hepatocyte-specific Glut9 knockout mice, allopurinol intervention, and acute UA administration in wild-type mice to assess dextran sulfate sodium (DSS)-induced acute colitis. Lamina propria immune cells were profiled by expanded flow cytometry; phagocytic/macrophage-lineage and NLRP3 pathways were perturbed with clodronate liposomes, MCC950, and Nlrp3 siRNA. Bone marrow-derived macrophages (BMDMs) and public human IBD mucosal transcriptomic datasets were analyzed. Results Glut9 HKO mice developed higher serum UA and more severe DSS-induced colitis than controls, whereas allopurinol reduced serum UA and ameliorated disease. Acute UA administration during DSS exposure similarly worsened colitis in wild-type mice. Hyperuricemia expanded colonic monocyte/macrophage-lineage cells during DSS challenge, increased pro-inflammatory cells, and enhanced NLRP3 inflammasome-associated signaling. Clodronate-sensitive macrophage depletion and MCC950 attenuated disease severity. In BMDMs, soluble UA enhanced LPS-primed inflammatory activation and inflammasome-associated readouts, which were reduced by NLRP3 inhibition or knockdown. In human IBD mucosal transcriptomic datasets, purine metabolism scores positively correlated with inflammatory macrophage and NLRP3 inflammasome signatures. Conclusions Elevated UA aggravates DSS-induced acute colitis and amplifies inflammatory monocyte/macrophage-lineage responses associated with NLRP3 inflammasome signaling. These findings identify hyperuricemia as a metabolic modifier of acute intestinal injury and support further investigation of UA-linked innate immune activation in IBD.
Reference Key
openalex_W7224016017 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Junyi Ji, Yize Wang, Tianyu Zhou, Jie Zhang, Zixin Xu, Zhe Shen, Chaohui Yu
Journal inflammatory bowel diseases
Year 2026
DOI
10.1093/ibd/izag227
URL
https://doi.org/10.1093/ibd/izag227
Keywords Keywords not found

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.